DESCRIPTION: Anorexia Nervosa (AN) is a serious psychiatric illness that is characterized by significant weight loss, hormonal disturbance reflected in amenorrhea, and cognitive distortions about body weight and shape. The purpose of this Mentored Patient-Oriented Research Career Development Award (MPORCDA), is to develop and execute a program of research that will investigate biological disturbances and associated clinical symptoms in women with AN, in order to elucidate some of the factors which may contribute to the development, as well as the high degree of tenacity, of this disorder. Specifically, it will test the hypotheses that 1) normal-weight women with history of AN have higher measures of serotonin, as evidenced by plasma tryptophan levels, and CSF 5-HIAA than age- and weight-matched healthy control women; 2) recently weight-restored women with AN will have lower measures of serotonin and its activity than will long-term weight restored women, as evidenced by plasma tryptophan, CSF 5-HIAA, and tryptophan-depletion challenge; and 3) long-term weight restored women will have evidence of lower serotonin transporter (SERT) binding potential (BP) as measured by PET study, compared with healthy controls, presumably because higher neurochemical levels led to down-regulation of receptor concentration. Under the strong mentorship of individuals with expertise in clinical research training and AN, neuroscience (specifically serotonergic activity and its assessment), and consultation from individuals with expertise in psychobiology of eating disorders, in brain imaging, in biology of eating and feeding behavior, and in the role of serotonin in gastrointestinal function, this MPORCDA will provide the candidate with the skills and further experience to integrate the advances of the fields of anorexia nervosa, neuroscience and biological psychiatry. The long-term goal of this award is for the candidate to become an expert and independent researcher in the psychobiology of eating disorders, with special application to anorexia nervosa.